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Lymphoid Cells and Tissues01:18

Lymphoid Cells and Tissues

Lymphoid cells and tissues are integral to the immune system, which is crucial in maintaining our body's defense against harmful pathogens. They form the building blocks of lymphoid organs, which include the spleen, thymus, and lymph nodes.
Lymphoid cells consist of various types of immune system cells. These include B and T lymphocytes, which are responsible for producing antibodies and killing infected cells, respectively. Dendritic cells act as messengers between the innate and adaptive...

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Multidimensional single-cell analysis reveals immune dysfunction and inflammatory response in lymphatic

Chunxiao Chen1,2, Wenhao Ju3, Xueying Li2

  • 1Vascular Anomalies and Vascular Interventional Center, Capital Center for Children's Health, Capital Medical University, Capital Institute of Pediatrics, Beijing 100020, China.

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Summary

Lymphatic malformations (LMs) involve immune cell dysfunction, with increased inflammatory monocytes and B cells, and decreased cytotoxic T and NK cells. Targeting S100A8 shows promise for treating these debilitating diseases.

Keywords:
immune dysfunctioninflammatory responselymphatic malformationssingle-cell RNA sequencing

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Area of Science:

  • Immunology
  • Molecular Biology
  • Genetics

Background:

  • Lymphatic malformations (LMs) are severe diseases with poorly understood immune system involvement.
  • The molecular mechanisms driving immune dysregulation in LMs require further elucidation.

Purpose of the Study:

  • To comprehensively characterize the immune cell landscape and molecular mechanisms in patients with LMs.
  • To identify potential therapeutic targets for LMs based on immune profiling.

Main Methods:

  • Integrated single-cell RNA, T-cell receptor, and B-cell receptor sequencing (scRNA-seq, scTCR-seq, scBCR-seq) were performed on peripheral blood and pleural effusion from LM patients.
  • Functional analyses were conducted to assess antigen processing, presentation, and transcription factor activity.
  • Repertoire analysis of T-cell receptors (TCRs) and B-cell receptors (BCRs) was performed.

Main Results:

  • Expansion of pro-inflammatory CD14+CD16+ monocytes and atypical memory B cells, alongside a reduction in cytotoxic CD8+ T and NK cells.
  • Impaired antigen processing/presentation in monocytes and dysregulated transcription factor activity were observed.
  • Significant remodeling of TCR and BCR repertoires, altered CXCL16-CXCR6 signaling, and upregulation of HLA-E:CD94-NKG2A impacting NK cell activity.
  • Identification of a pro-inflammatory monocyte program and S100A8 as a potential therapeutic target.

Conclusions:

  • LMs are characterized by specific immune cell dysregulation, including monocyte and lymphocyte abnormalities.
  • S100A8 is a promising therapeutic target, as its inhibition ameliorated the pathological LM phenotype.
  • These findings provide critical insights into LM pathogenesis and potential avenues for treatment.